Search PubMed⌕ Search

Biomedical subjects

E D Kilbourne

Publications and source records attributed to E D Kilbourne.

102 records · Page 6Linked to original sources
PubMed1966

The influence of cortisone on experimental viral infection. VI. Inhibition by hydrocortisone of interferon synthesis in the chick embryo.

The initial observations that cortisone may act as an inhibitor of viral interference (11, 4) are now explicable as an inhibitory effect on interferon synthesis. The suggestion that the action of interferon is also inhibited by cortisone or its analogues (6) has not been confirmed in a plaque reduction type of interferon assay system in which autointerference by the challenge inoculum is a lesser problem. In this respect, the present results are in accord with those obtained by DeMaeyer and DeMaeyer (8) with hydrocortisone in a system in which a low multiplicity (0.1) Sindbis virus infection in monolayer culture was employed with cytopathic effect (CPE) as an end-point. It has been shown that hydrocortisone is restrictive to the synthesis of interferon induced by inoculation of either infective or inactivated virus into the chick embryo, and that this inhibitory effect is temporary. However, in another study in the chick embryo, three spaced injections of hydrocortisone (0.25 mg/dose) prevented the appearance of detectable interferon during the entire 64 hr observation period following inoculation of 10(3.3) EID(50) of Lee virus (12). The importance of explicit definition of experimental conditions in assessing hormonal effects on infection is illustrated by the capacity of hydrocortisone either to inhibit or increase interferon synthesis in vitro, depending on the proportion of inactivated and infective virus in the inoculum employed, and the time at which interferon is measured. As suggested previously, it is not unlikely that similar shifts in hormone-virus-interferon balance may operate in vivo to influence the outcome of infection.

Animals↗
PubMed1966

The influence of cortisone on experimental viral infection. VII. Kinetics of interferon formation and its inhibition with hydrocortisone in relation to viral strain and virulence.

A comparative study was undertaken of the pathogenesis of infection of the allantoic sac of the chick embryo with three influenza viruses of differing virulence, and of the influence of hydrocortisone on the course of infection. Judged on the basis of earlier onset and greater degree of inflammatory response and diminished survival time of infected embryos, Mel. and Lee viruses were markedly more virulent than PR8, despite the earlier appearance of virus in PR8-infected embryos. Interferon appeared first and in greater quantity in the allantoic fluid of Lee-infected embryos and latest with PR8 infection. Thus, there was no correlation of avirulence and better interferon production with the viruses under study in the present system. Furthermore, evidence obtained suggested that Lee virus ("virulent") was most susceptible to interferon action, and also that viral synthesis in the chorioallantoic membrane with PR8 ("avirulent") persisted after the appearance of interferon. The injection of hydrocortisone within 2 hr of the initiation of infection delayed the synthesis of all three viruses; had no significant effect upon the inflammatory response; and transiently inhibited the synthesis of interferon, while prolonging the survival of Lee- and Mel.-infected embryos. Late administration of hydrocortisone suppresses both the inflammatory response and the production of interferon. Only in the case of Lee virus infection did hydrocortisone administration lead to augmentation of final yields of virus with the low infection multiplicity employed in the present experiments. It is postulated that Lee virus is a better inducer of interferon because its infectivity in vivo is more rapidly inactivated. As a consequence synthesis of Lee virus is more under the control of endogenous interferon than is the case with PR8 or Mel. virus. Therefore, inhibition of interferon synthesis with hydrocortisone has a greater influence on final yields of Lee virus.

Animals↗
PubMed1966

Discussion.

Explore the source record for details and available documents.

Journal Article↗
PubMed1966

Reduction in plaque size and reduction in plaque number as differing indices of influenza virus-antibody reactions.

Jahiel, R. I. (Cornell University Medical College, New York, N.Y.), and E. D. Kilbourne. Reduction in plaque size and reduction in plaque number as differing indices of influenza virus-antibody reactions. J. Bacteriol. 92:1521-1534. 1966.-The serological reactivity of an antigenically hybrid influenza virus recombinant (X-7) was studied in a heteroploid cell plaquing system in which antisera to the parental viruses NWS/(A(0)) and RI/5(+) (A(2)) were incorporated in agar overlay media. Two different effects on plaque formation were found. With NWS antiserum, there was close relationship between reduction in plaque size and in plaque number [plaque inhibition (PI) pattern]. With RI/5 antiserum, plaque size reduction (PSR) occurred over a wide zone of serum dilutions without concomitant change in plaque number (PSR pattern). Several different preinoculation neutralization tests showed a strong reactivity of X-7 with NWS antisera and little if any reactivity with RI/5 antisera. We interpret the differing effects of NWS and RI/5 antisera on X-7 as indicative of the possible occurrence of different mechanisms of neutralization or of the possible participation of different surface antigens. The kinetics of PSR are consistent with the hypothesis that it results from the reaction of RI/5 antiserum with the RI/5-like neuraminidase of X-7. Studies with the antiserum-in-overlay technique of PSR and PI patterns comprise a sensitive method for quantitative antigenic analysis of plaque-forming influenza viruses.

Antibodies↗
PubMedDate not supplied

Supplementation of conventional influenza A vaccine with purified viral neuraminidase results in a balanced and broadened immune response.

Influenza virus neuraminidase was chromatographically extracted from A/Johannesburg/33/94 (H3N2) and used to supplement conventional monovalent H3JHN2JH inactivated influenza vaccine. Immunization of mice with this preparation resulted in high titers of antibodies to both hemagglutinin (HA) and neuraminidase (NA) equivalent for each antigen to titers in animals immunized with either antigen alone. Homotypic infection was suppressed and greater reduction in viral replication was observed following heterotypic infectious challenge than was observed following the non-supplemented vaccine. There was no evidence of suppression of the immune response to the HA despite the presence of high amounts of NA in the vaccine. Supplementation of conventional inactivated influenza vaccine with NA takes advantage of the equivalent immunogenicity of dissociated HA and NA, to produce a more balanced immune response to both surface antigens, without the antigenic competition tht occurs after immunization with conventional vaccine or infection. These studies in a mouse model system suggest that supplementation of current inactivated influenza vaccines offers the prospect of improved immunization of humans against influenza.

Animals↗
PubMedDate not supplied

Recent contributions of molecular biology to the clinical virology of myxoviruses.

Recent advances in the clinical virology of influenza are based on non-pragmatically oriented research on the genetics and biochemistry of the influenza virus. Antigenically hybrid recombinant viruses can be tailored to provide monospecific reagents for serological studies. Basic research on viral structure and the mechanism of viral replication has directly influenced the establishment of a cell culture system suitable for the isolation of most influenza viruses. Identification of viral genotype by RNA gel electrophoresis and mapping of oligonucleotides of viral RNA has already facilitated epidemiologic investigations. The clinical virologist of the future must have an understanding of the potential limitations of these techniques for specific strain identification.

Genes, Viral↗
PubMedDate not supplied

The emergence of "emerging diseases": a lesson in holistic epidemiology.

The term "emerging diseases" is a loosely defined category of entities comprising resurgent or recurrent old diseases (usually caused by "new" or mutated previously known agents), diseases truly new to man, but caused by preexisting ("old") zoonotic agents, and syndromes newly defined by the discovery of new agents through advances in biotechnology. Identification and solution of these problems depends, first, on recognition of their differences, and then upon tailoring appropriate strategies for their control. Thus, new influenza viruses appear each year to challenge immunity to their antecedents, but evoke the unchanged and centuries old symptom complex of influenza. Tuberculosis, is resurgent because of mycobacterial mutation to antibiotic resistance, immunosuppression by AIDS, and laxity in public health surveillance. Parvovirus B19 and herpesvirus 6 were revealed as cryptic infectors of white blood cells in studies of hepatitis B and AIDS, but since have been shown to be important causes of childhood rashes, aplastic anemia, and neurologic disease. The encroachment of human habitation on wilderness perimeters (ecosystem change) has increased contact with vectors of zoonotic viruses and bacteria, as evidenced by Lyme disease, Ebola virus infection, and the hemorrhagic fevers. The term "holistic epidemiology" embraces all these problems, from the molecular to the macroenvironmental level. Humans, parasites, and their environment will continue their ancient, fluctuating, dynamic relationship in the future, and new diseases will continue to emerge.

Communicable Disease Control↗